The activation process of T lymphocytes was characterized from an intracellular, molecular point of view. The c-myc oncogene, the interleukin-2 (IL-2) growth factor and the IL-2 receptor gene are known to be induced during the early activation of T cells. We have determined regulatory regions within the chromatin structure of these genes, which will allow us to dissect the nuclear molecular events resulting from the transmission of the extracellular activation signal. Along the same lines, a model system has been developed to study the effect of differentiation at the nuclear level. The promyelocytic leukemia cell line HL60 can be differentiated terminally in vitro. Concomitantly, the c-myc oncogene is downregulated and its chromatin changes dramatically. We have initiated also more broadly based studies directed at the activation process of T cells. cDNA libraries were made from activated peripheral blood T cells in order to identify genes which are specifically and immediately induced upon mitogenic stimultion. A similar approach has been utilized in order to identify the genes coding for the lymphokines which are elaborated by these T cells after stimulation and in particular to identify the gene for the well-characterized B cell growth factor (BCGF). Gene cloning from this factor has been pursued also by preparing distinct cDNA libraries from a B cell tumor which expresses it constitutively. These libraries allow screening for the growth factor by two methods: one is based on partial amino acid sequence information of the purified growth factor, and the other method is based on the detection of BCGF by polyclonal antibodies in an expression library.